Infection of Ferrets with Influenza Virus Elicits a Light Chain-Biased Antibody Response against Hemagglutinin

The domestic ferret (Mustela putorius furo) is a commonly used animal model for the study of influenza virus infection and vaccination. Recently, our group has developed murine mAbs with specificity for the kappa (Ig kappa) and lambda (Ig lambda) L chains of ferret Ig. These mAbs were used to quantify the abundance of Ig kappa and Ig lambda in serum and to evaluate L chain usage of the Ab response against the hemagglutinin (HA) protein elicited by influenza infection. After influenza A infection of immunologically naive ferrets with various HlNl or H3N2 strains, the acute Ab response against HA exhibited an inherent bias toward lambda L chain usage. In contrast, secondary infection of HlNl preimmune ferrets with an antigenically distinct HlNl virus elicited a recall response against the original HA that was no longer biased toward Ig lambda and possessed differential specificity. Moreover, sequential infection of ferrets with HlNl influenza viruses elicited an Ig kappa-biased Ab response directed against the HA globular head and stem regions. Furthermore, sequential infection of ferrets with viral vectors expressing chimeric HA, aimed at boosting Ab reactivity against the HA stem region, also elicited an Ig kappa-biased response. Collectively, these findings suggest that ferret B cells expressing an Ig kappa or Ig lambda BCR possess differential specificities, and highlight the utility of our recently developed mAbs for studying the immune response to influenza virus infection and vaccination in the ferret model.